1. Bhat RS, Chandrul KK, El-Ansary A. {{Beneficial Effects of a Protein Rich Diet on Coping Neurotrans-mitter Levels During Ampicillin-Induced Neurotoxicity Compared to Propionic-Acid Induced Autistic Biochemical Features}}. {Int J Mol Cell Med};2016 (Summer);5(3):149-159.
This study examined the effects of a protein rich diet on coping neurotransmitter levels in orally administered ampicillin-induced neurotoxic rats compared with propionic acid (PA) models of autism. 40 young male western albino rats were divided into four groups. The first group served as control and received phosphate buffered saline orally; the second group serving as autistic model was treated with oral dose of PA (250 mg/kg body weight/day for 3 days); the third group was treated with the neurotoxic dose of ampicillin (50 mg/kg for three weeks); the fourth group received the same dose of ampicillin and was fed with special protein rich diets. Noradrenaline, dopamine, serotonin glutamate, glutamine and interleukin 6 (IL-6) were measured in the brain homogenate of all tested groups. Specified doses of PA and ampicillin significantly (P<0.001) decreased noradrenaline, dopamine, and serotonin levels when compared to control. Also glutamate, IL-6 levels were significantly (P<0.001) increased in PA treated group while non-significant increase was found in ampicillin treated group. Non-significant increase of glutamine was found in PA treated group with a significant increase in ampicillin treated group. The effects of ampicillin on these parameters were found to be potentiated when the rats were fed on a protein rich diet. Our results end with the conclusion that dietary protein level may be a useful tool to find out a path to restrict neurotransmitter alterations in neurodevelopmental disorders like autism. Lien vers Pubmed
2. Cooper RA, Plaisted-Grant KC, Baron-Cohen S, Simons JS. {{Eye movements reveal a dissociation between memory encoding and retrieval in adults with autism}}. {Cognition};2016 (Dec 08);159:127-138.
People with Autism Spectrum Disorder (ASD) exhibit subtle deficits in recollection, which have been proposed to arise from encoding impairments, though a direct link has yet to be demonstrated. In the current study, we used eye-tracking to obtain trial-specific measures of encoding (eye movement patterns) during incidental (natural viewing) and intentional (strategic) encoding conditions in adults with ASD and typical controls. Using this approach, we tested the degree to which differences in encoding might contribute to recollection impairments, or whether group differences in memory primarily emerge at retrieval. Following encoding of scenes, participants were asked to distinguish between old and similar lure scenes and provide ‘remember’/’familiar’ responses. Intentional encoding increased eye movements and subsequent recollection in both groups to a similar degree, but the ASD group were impaired overall at the memory task and used recollection less frequently. In controls, eye movements at encoding predicted subsequent correct responses and subsequent recollection on a trial-by-trial basis, as expected. In contrast, despite a similar pattern of eye movements during encoding in the two groups, eye movements did not predict trial-by-trial subsequent memory in ASD. Furthermore, recollection was associated with lower similarity between encoding- and retrieval-related eye movements in the ASD group compared to the control group. The eye-tracking results therefore provide novel evidence for a dissociation between encoding and recollection-based retrieval in ASD.
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3. Dunaway KW, Islam MS, Coulson RL, Lopez SJ, Vogel Ciernia A, Chu RG, Yasui DH, Pessah IN, Lott P, Mordaunt C, Meguro-Horike M, Horike SI, Korf I, LaSalle JM. {{Cumulative Impact of Polychlorinated Biphenyl and Large Chromosomal Duplications on DNA Methylation, Chromatin, and Expression of Autism Candidate Genes}}. {Cell Rep};2016 (Dec 13);17(11):3035-3048.
Rare variants enriched for functions in chromatin regulation and neuronal synapses have been linked to autism. How chromatin and DNA methylation interact with environmental exposures at synaptic genes in autism etiologies is currently unclear. Using whole-genome bisulfite sequencing in brain tissue and a neuronal cell culture model carrying a 15q11.2-q13.3 maternal duplication, we find that significant global DNA hypomethylation is enriched over autism candidate genes and affects gene expression. The cumulative effect of multiple chromosomal duplications and exposure to the pervasive persistent organic pollutant PCB 95 altered methylation of more than 1,000 genes. Hypomethylated genes were enriched for H2A.Z, increased maternal UBE3A in Dup15q corresponded to reduced levels of RING1B, and bivalently modified H2A.Z was altered by PCB 95 and duplication. These results demonstrate the compounding effects of genetic and environmental insults on the neuronal methylome that converge upon dysregulation of chromatin and synaptic genes.
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4. Duvekot J, van der Ende J, Verhulst FC, Slappendel G, van Daalen E, Maras A, Greaves-Lord K. {{Factors influencing the probability of a diagnosis of autism spectrum disorder in girls versus boys}}. {Autism};2016 (Dec 09)
In order to shed more light on why referred girls are less likely to be diagnosed with autism spectrum disorder than boys, this study examined whether behavioral characteristics influence the probability of an autism spectrum disorder diagnosis differently in girls versus boys derived from a multicenter sample of consecutively referred children aged 2.5-10 years. Based on information from the short version of the Developmental, Dimensional and Diagnostic Interview and the Autism Diagnostic Observation Schedule, 130 children (106 boys and 24 girls) received a diagnosis of autism spectrum disorder according to Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) criteria and 101 children (61 boys and 40 girls) did not. Higher overall levels of parent-reported repetitive and restricted behavior symptoms were less predictive of an autism spectrum disorder diagnosis in girls than in boys (odds ratio interaction = 0.41, 95% confidence interval = 0.18-0.92, p = 0.03). In contrast, higher overall levels of parent-reported emotional and behavioral problems increased the probability of an autism spectrum disorder diagnosis more in girls than in boys (odds ratio interaction = 2.44, 95% confidence interval = 1.13-5.29, p = 0.02). No differences were found between girls and boys in the prediction of an autism spectrum disorder diagnosis by overall autistic impairment, sensory symptoms, and cognitive functioning. These findings provide insight into possible explanations for the assumed underidentification of autism spectrum disorder in girls in the clinic.
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5. Fecteau SM, Boivin L, Trudel M, Corbett BA, Harrell FE, Jr., Viau R, Champagne N, Picard F. {{Parenting stress and salivary cortisol in parents of children with autism spectrum disorder: Longitudinal variations in the context of a service dog’s presence in the family}}. {Biol Psychol};2016 (Dec 13)
A significant portion of parents of children with autism spectrum disorder report high levels of stress related to parenting responsibilities, which have been linked to abnormal cortisol patterns. This study seeks to better understand the parents’ adaptation to caregiving demands and use of a service dog, by taking into account longitudinal variations in salivary cortisol and perception of parental stress. Salivary cortisol was collected one day per week for 15 weeks by 98 primary caregivers of children with ASD. Overall, parents perceived high levels of stress at baseline. Mean morning cortisol increase was below expected levels for healthy adults, and perception of stress predicted morning cortisol activity. Hypocorticolism related to chronic stress may be present in parents of children with ASD. Longitudinal analysis revealed that the presence of a service dog in the family had an effect on parenting stress, wakening and morning cortisol levels.
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6. Ho KS, Wassman ER, Baxter AL, Hensel CH, Martin MM, Prasad A, Twede H, Vanzo RJ, Butler MG. {{Chromosomal Microarray Analysis of Consecutive Individuals with Autism Spectrum Disorders Using an Ultra-High Resolution Chromosomal Microarray Optimized for Neurodevelopmental Disorders}}. {Int J Mol Sci};2016 (Dec 09);17(12)
Copy number variants (CNVs) detected by chromosomal microarray analysis (CMA) significantly contribute to understanding the etiology of autism spectrum disorder (ASD) and other related conditions. In recognition of the value of CMA testing and its impact on medical management, CMA is in medical guidelines as a first-tier test in the evaluation of children with these disorders. As CMA becomes adopted into routine care for these patients, it becomes increasingly important to report these clinical findings. This study summarizes the results of over 4 years of CMA testing by a CLIA-certified clinical testing laboratory. Using a 2.8 million probe microarray optimized for the detection of CNVs associated with neurodevelopmental disorders, we report an overall CNV detection rate of 28.1% in 10,351 consecutive patients, which rises to nearly 33% in cases without ASD, with only developmental delay/intellectual disability (DD/ID) and/or multiple congenital anomalies (MCA). The overall detection rate for individuals with ASD is also significant at 24.4%. The detection rate and pathogenic yield of CMA vary significantly with the indications for testing, age, and gender, as well as the specialty of the ordering doctor. We note discrete differences in the most common recurrent CNVs found in individuals with or without a diagnosis of ASD.
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7. Ipci M, Inci SB, Akyol Ardic U, Ercan ES. {{A Case of Asperger Syndrome With Comorbidity of Posttraumatic Stress Disorder and Selective Mutism: Significant Remission With the Combination of Aripiprazole and Eye Movement Desensitization and Reprocessing}}. {J Clin Psychopharmacol};2016 (Dec 13)
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8. Lachowska M, Pastuszka A, Lukaszewicz-Moszynska Z, Mikolajewska L, Niemczyk K. {{Cochlear implantation in autistic children with profound sensorineural hearing loss}}. {Braz J Otorhinolaryngol};2016 (Nov 19)
INTRODUCTION: Cochlear implants have become the method of choice for the treatment of severe-to-profound hearing loss in both children and adults. Its benefits are well documented in the pediatric and adult population. Also deaf children with additional needs, including autism, have been covered by this treatment. OBJECTIVE: The aim of this study was to assess the benefits from cochlear implantation in deafened children with autism as the only additional disability. METHODS: This study analyzes data of six children. The follow-up time was at least 43 months. The following data were analyzed: medical history, reaction to music and sound, Ling’s six sounds test, onomatopoeic word test, reaction to spoken child’s name, response to requests, questionnaire given to parents, sound processor fitting sessions and data. RESULTS: After cochlear implantation each child presented other communication skills. In some children, the symptoms of speech understanding were observed. No increased hyperactivity associated with daily use cochlear implant was observed. The study showed that in autistic children the perception is very important for a child’s sense of security and makes contact with parents easier. CONCLUSION: Our study showed that oral communication is not likely to be a realistic goal in children with cochlear implants and autism. The implantation results showed benefits that varied among those children. The traditional methods of evaluating the results of cochlear implantation in children with autism are usually insufficient to fully assess the functional benefits. These benefits should be assessed in a more comprehensive manner taking into account the limitations of communication resulting from the essence of autism. It is important that we share knowledge about these complex children with cochlear implants.
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9. LaFauci G, Adayev T, Kascsak R, Brown WT. {{Detection and Quantification of the Fragile X Mental Retardation Protein 1 (FMRP)}}. {Genes (Basel)};2016 (Dec 09);7(12)
The final product of FMR1 gene transcription, Fragile X Mental Retardation Protein 1 (FMRP), is an RNA binding protein that acts as a repressor of translation. FMRP is expressed in several tissues and plays important roles in neurogenesis, synaptic plasticity, and ovarian functions and has been implicated in a number of neuropsychological disorders. The loss of FMRP causes Fragile X Syndrome (FXS). In most cases, FXS is due to large expansions of a CGG repeat in FMR1-normally containing 6-54 repeats-to over 200 CGGs and identified as full mutation (FM). Hypermethylation of the repeat induces FMR1 silencing and lack of FMRP expression in FM male. Mosaic FM males express low levels of FMRP and present a less severe phenotype that inversely correlates with FMRP levels. Carriers of pre-mutations (55-200 CGG) show increased mRNA, and normal to reduced FMRP levels. Alternative splicing of FMR1 mRNA results in 24 FMRP predicted isoforms whose expression are tissues and developmentally regulated. Here, we summarize the approaches used by several laboratories including our own to (a) detect and estimate the amount of FMRP in different tissues, developmental stages and various pathologies; and (b) to accurately quantifying FMRP for a direct diagnosis of FXS in adults and newborns.
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10. Lemaire-Mayo V, Subashi E, Henkous N, Beracochea D, Pietropaolo S. {{Behavioral effects of chronic stress in the Fmr1 mouse model for fragile X syndrome}}. {Behav Brain Res};2016 (Dec 06);320:128-135.
Fragile X Syndrome (FXS) is a pervasive developmental disorder due to a mutation in the FMR1 X-linked gene. Despite its clear genetic cause, the expression of FXS symptoms is known to be modulated by environmental factors, including stress. Furthermore, several studies have shown disturbances in stress regulatory systems in FXS patients and Fmr1 mice. These studies have mostly focused on the hormonal responses to stress, using the acute exposure to a single type of stressor. Hence, little is known about the behavioral effects of stress in FXS, and the importance of the nature of the stressing procedure, especially in the context of a repeated exposure that more closely resembles real life conditions. Here we evaluated the effects of chronic exposure to different types of stress (i.e., either repeated restraint or unpredictable stress) on the behavioral phenotype of adult Fmr1 mice. Our results demonstrated that chronic stress induced deficits in social interaction and working memory only in WT mice and the impact of stress depended on the type of stressors and the specific behavior tested. Our data suggest that the behavioral sensitivity to stress is dramatically reduced in FXS, opening new views on the impact of gene-environment interactions in this pathology.
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11. Li K, Jiang XD, Li F. {{[Gastrointestinal difficulties in children with autism spectrum disorder]}}. {Zhonghua Er Ke Za Zhi};2016 (Dec 02);54(12):957-960.
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12. Morales-Suarez-Varela M, Peraita-Costa I, Llopis-Gonzalez A. {{Systematic review of the association between particulate matter exposure and autism spectrum disorders}}. {Environ Res};2016 (Dec 13);153:150-160.
Particulate matter (PM) as an environmental pollutant is suspected to be associated with autism spectrum disorders. The aim of the present study was to review the epidemiological literature currently available on the relation between PM exposure and diagnosis of ASD. The PubMed database was searched from November 2015 up to January 2016 by one of the authors. We included observational studies (cohort and case-control studies) published in English carried out in children within the last 10 years, measuring PM exposure and health outcomes related to ASD. 13 studies met the inclusion criteria. Four of the studies found no association between PM exposure and ASD. The other 8 studies show positive associations restricted to specific exposure windows which however do not reach statistical significance at times. To conclude, the evidence from the studies allows us to conclude that there is an association between PM exposure and ASD whose strength varies according to the particle size studied with the association with PM2.5 and diesel PM being stronger. Given the potential importance for public health, cohort studies with proper adjustment for confounding variables and identification of critical windows of exposure are urgently needed to further improve knowledge about potential causal links between PM exposure and the development of ASD.
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13. Packer A. {{Enrichment of factors regulating canonical Wnt signaling among autism risk genes}}. {Mol Psychiatry};2016 (Dec 13)
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14. Rubinstein M, Patowary A, Stanaway IB, McCord E, Nesbitt RR, Archer M, Scheuer T, Nickerson D, Raskind WH, Wijsman EM, Bernier R, Catterall WA, Brkanac Z. {{Association of rare missense variants in the second intracellular loop of NaV1.7 sodium channels with familial autism}}. {Mol Psychiatry};2016 (Dec 13)
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder often accompanied by intellectual disability, language impairment and medical co-morbidities. The heritability of autism is high and multiple genes have been implicated as causal. However, most of these genes have been identified in de novo cases. To further the understanding of familial autism, we performed whole-exome sequencing on five families in which second- and third-degree relatives were affected. By focusing on novel and protein-altering variants, we identified a small set of candidate genes. Among these, a novel private missense C1143F variant in the second intracellular loop of the voltage-gated sodium channel NaV1.7, encoded by the SCN9A gene, was identified in one family. Through electrophysiological analysis, we show that NaV1.7C1143F exhibits partial loss-of-function effects, resulting in slower recovery from inactivation and decreased excitability in cultured cortical neurons. Furthermore, for the same intracellular loop of NaV1.7, we found an excess of rare variants in a case-control variant-burden study. Functional analysis of one of these variants, M932L/V991L, also demonstrated reduced firing in cortical neurons. However, although this variant is rare in Caucasians, it is frequent in Latino population, suggesting that genetic background can alter its effects on phenotype. Although the involvement of the SCN1A and SCN2A genes encoding NaV1.1 and NaV1.2 channels in de novo ASD has previously been demonstrated, our study indicates the involvement of inherited SCN9A variants and partial loss-of-function of NaV1.7 channels in the etiology of rare familial ASD.Molecular Psychiatry advance online publication, 13 December 2016; doi:10.1038/mp.2016.222.
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15. Shelton AL, Cornish KM, Kolbe S, Clough M, Slater HR, Li X, Kraan CM, Bui QM, Godler DE, Fielding J. {{Brain structure and intragenic DNA methylation are correlated, and predict executive dysfunction in fragile X premutation females}}. {Transl Psychiatry};2016 (Dec 13);6(12):e984.
DNA methylation of the Fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary has been associated with executive dysfunction in female carriers of a FMR1 premutation (PM: 55-199 CGG repeats), whereas neuroanatomical changes have been associated with executive dysfunction in PM males. To our knowledge, this study for the first time examined the inter-relationships between executive function, neuroanatomical structure and molecular measures (DNA methylation and FMR1 mRNA levels in blood) in PM and control (<44 CGG repeats) females. In the PM group, FMR1 intron 1 methylation was positively associated with executive function and cortical thickness in middle and superior frontal gyri, and left inferior parietal gyrus. By contrast, in the control group, FMR1 intron 1 methylation was negatively associated with cortical thickness of the left middle frontal gyrus and superior frontal gyri. No significant associations were revealed for either group between FMR1 mRNA and neuroanatomical structure or executive function. In the PM group, the lack of any significant association between FMR1 mRNA levels and phenotypic measures found in this study suggests that either FMR1 expression is not well conserved between tissues, or that FMR1 intron 1 methylation is linked to neuroanatomical and cognitive phenotype in PM females via a different mechanism. Lien vers le texte intégral (Open Access ou abonnement)
16. Valencia-Naranjo N, Robles-Bello MA. {{Learning potential and cognitive abilities in preschool boys with fragile X and Down syndrome}}. {Res Dev Disabil};2016 (Dec 13);60:153-161.
BACKGROUND: Enhancing cognitive abilities is relevant when devising treatment plans. AIMS: This study examined the performance of preschool boys with Down syndrome and fragile X syndrome in cognitive tasks (e.g., nonverbal reasoning and short-term memory), as well as in improving cognitive functions by means of a learning potential methodology. METHODS AND PROCEDURES: The basic scales corresponding to the Skills and Learning Potential Preschool Scale were administered to children with Down syndrome and others with fragile X syndrome, matched for chronological age and nonverbal cognitive development level. RESULTS: The fragile X syndrome group showed stronger performance on short-term memory tasks than the Down syndrome group prior to intervention, with no differences recorded in nonverbal reasoning tasks. In addition, both groups’ cognitive performance improved significantly between pre- and post-intervention. However, learning potential relative to auditory memory was limited in both groups, and for rule-based categorization in Down syndrome children. CONCLUSION: The scale offered the opportunity to assess young children’s abilities and identify the degree of cognitive modifiability. Furthermore, factors that may potentially affect the children’s performance before and during learning potential assessment are discussed.
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17. Zajic MC, McIntyre N, Swain-Lerro L, Novotny S, Oswald T, Mundy P. {{Attention and written expression in school-age, high-functioning children with autism spectrum disorders}}. {Autism};2016 (Dec 09)
High-functioning children with autism spectrum disorders often find writing challenging. These writing difficulties may be specific to autism spectrum disorder or to a more general clinical effect of attention disturbance, as these children are often comorbid for attention-deficit/hyperactivity disorder (ADHD) symptomatology (and children with attention-deficit/hyperactivity disorder often also find writing challenging). To examine this issue, this study investigated the role of attention disturbance on writing in 155 school-age children across four diagnostic groups: high-functioning autism spectrum disorder (HFASD) with lower ADHD symptoms (HFASD-L), HFASD with higher ADHD symptoms (HFASD-H), ADHD symptoms but no autism spectrum disorder symptoms, and typical development. Both HFASD subgroups and the ADHD group displayed lower word production writing scores than the typical development group, but the clinical groups did not differ. The HFASD-H and ADHD groups had significantly lower theme development and text organization writing scores than the typical development group, but the HFASD-L and typical development groups were not significantly different. The findings support prior research reporting writing problems in children with autism spectrum disorder but also suggest that children with HFASD-H may be at greater risk for writing difficulties than children with HFASD-L. Better understanding the role of attention in writing development could advance methods for assessment and intervention for children with high-functioning autism spectrum disorder at risk for writing difficulties.
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18. Zhu Z, Lu X, Yuan D, Huang S. {{Close genetic relationships between a spousal pair with autism-affected children and high minor allele content in cases in autism-associated SNPs}}. {Genomics};2016 (Dec 08)
Parents of children affected with autism spectrum disorders (ASD) often have mild forms of autistic-like characteristics. Past studies have focused on searching for individual genetic risk loci of ASD. Here we studied the overall properties of the genomes of ASD trios by using previously published genome-wide data for common SNPs. The pairwise genetic distance (PGD) between a spousal pair with ASD-affected children was found smaller than that of a random pair selected among the spouses in the ASD trios, and spousal relatedness correlated with severe forms of ASD. Furthermore, for a set of 970 ASD associated SNPs, cases showed higher homozygous minor allele content than parents. These results indicate new genetic elements in the broad phenotypes of parents with ASD-affected offspring and in ASD pathogenesis.
